What can cause a false positive Tricyclic Antidepressant (TCA) result on a urine drug screen?

From the Guidelines

Several medications and substances can cause false positive results for tricyclic antidepressants (TCAs) on urine drug screens, including certain antihistamines, quetiapine, carbamazepine, cyclobenzaprine, and hydroxyzine. When interpreting urine drug screen results, it is essential to consider the patient's complete medication history to avoid misinterpreting false positives as evidence of TCA use. Some common culprits that may trigger false positives include:

• Certain antihistamines like diphenhydramine (Benadryl)
• Quetiapine (Seroquel)
• Carbamazepine (Tegretol)
• Cyclobenzaprine (Flexeril)
• Hydroxyzine (Atarax, Vistaril) Other medications that may cause false positives include sertraline (Zoloft) at high doses, phenothiazines like chlorpromazine, and the muscle relaxant orphenadrine, as noted in various studies 1. These false positives occur because immunoassay screening tests detect structural similarities between these compounds and TCAs rather than identifying the specific drug. The tests typically recognize the three-ring structure common to TCAs, which is also present in some other medications. When a positive TCA result is unexpected, clinicians should consider the patient's complete medication history and may need to order confirmatory testing using more specific methods like gas chromatography-mass spectrometry (GC-MS) or liquid chromatography-tandem mass spectrometry (LC-MS/MS) to verify the presence of actual TCAs. Understanding the type of drug test that a laboratory is using will inform interpretation of test results, and clinicians should be aware that rapid test results may not be definitive, as they may yield more false-positive results compared to confirmatory tests 1.

From the FDA Drug Label

There have been literature reports suggesting false positive results in urine enzyme immunoassays for methadone and tricyclic antidepressants in patients who have taken quetiapine. The use of quetiapine can cause a false positive Tricyclic Antidepressant (TCA) result on a urine drug screen, as reported in literature 2.

From the Research

Causes of False Positive Tricyclic Antidepressant (TCA) Results

• Diphenhydramine, a first-generation antihistamine medication, can cause false positive results for tricyclic antidepressants (TCAs) in urine examinations 3
• Carbamazepine ingestion can lead to false-positive tricyclic antidepressant serum toxic screen results 4
• Certain antipsychotic medications, antihistamines, and the muscle relaxant cyclobenzaprine can also cause false-positive tricyclic antidepressant toxic screen results 4
• Other substances that may cause false-positive results for TCAs include:
  • Antihistamines such as brompheniramine, diphenhydramine, and doxylamine 5
  • Antipsychotics such as chlorpromazine, quetiapine, and thioridazine 5
  • Antibiotics such as quinolones (ofloxacin and gatifloxacin) 5
  • Analgesics such as ibuprofen and naproxen 5
  • Nonprescription agents such as a nasal inhaler 5

Importance of Confirming Results

• False-positive results can be obtained from immunoassay tests, which are commonly used for urine drug screens 6, 5
• It is essential to confirm positive results using additional analytical methods, such as gas chromatography-mass spectrometry, to avoid adverse consequences for patients 6, 5